Methods and systems for adenovirus interaction with desmoglein 2 (DSG2)

Abstract

The present invention provides compositions, compounds, and methods relating to recombinant adenoviral-based polypeptides for treating disorders associated with epithelial tissues.

We claim:  
     
       1. A recombinant AdB-2/3 fiber polypeptide comprising the amino acid sequence of junction opener-1 (JO-1) (SEQ ID NO:20). 
     
     
       2. The recombinant AdB-2/3 fiber polypeptide of  claim 1 , wherein the AdB-2/3 fiber polypeptide is multimerized. 
     
     
       3. A composition, comprising (a) the recombinant AdB-2/3 fiber polypeptide of  claim 1 , and (b) one or more compounds selected from the group consisting of therapeutics, diagnostics, and imaging agents. 
     
     
       4. A recombinant AdB-2/3 fiber polypeptide, comprising:
 a) one or more AdB-2/3 fiber polypeptide shaft domains; and 
 b) an AdB-2/3 fiber polypeptide knob domain, operatively linked to and located C-terminal to the one or more AdB-2/3 fiber polypeptide shaft domains;
 wherein the recombinant AdB-2/3 fiber polypeptide is multimerized, and is capable of binding to desmoglein 2 (DSG2) on epithelial cells, 
 wherein the AdB-2/3 fiber polypeptide does not include an AdB-2/3 fiber polypeptide tail domain. 
 
 
     
     
       5. The recombinant AdB-2/3 fiber polypeptide of  claim 4 , wherein each shaft domain is selected from the group consisting of an Ad3 fiber polypeptide shaft domain, an Ad7 fiber polypeptide shaft domain, an Ad11 fiber polypeptide shaft domain, an Ad 14 fiber polypeptide shaft domain, an Ad14a fiber polypeptide shaft domain, and combinations thereof. 
     
     
       6. The recombinant AdB-2/3 fiber polypeptide of  claim 4 , wherein the one or more shaft domains comprise 1-22 shaft domains. 
     
     
       7. The recombinant AdB-2/3 fiber polypeptide of  claim 4 , wherein each shaft domain comprises an amino acid sequence according to SEQ ID NO: 11. 
     
     
       8. The recombinant AdB-2/3 fiber polypeptide of  claim 4 , wherein each shaft domain comprises an amino acid sequence according to SEQ ID NO: 12. 
     
     
       9. The recombinant AdB-2/3 fiber polypeptide of any  claim 4 , wherein each shaft domain comprises an amino acid sequence selected from the group consisting of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, and SEQ ID NO:5. 
     
     
       10. The recombinant AdB-2/3 fiber polypeptide of  claim 4 , wherein the knob domain is selected from the group consisting of an Ad3 fiber polypeptide knob domain, an Ad7 fiber polypeptide knob domain, an Ad11 fiber polypeptide knob domain, an Ad 14 fiber polypeptide knob domain, an Ad14a fiber polypeptide knob domain. 
     
     
       11. The recombinant AdB-2/3 fiber polypeptide of  claim 4 , wherein the knob domain comprises an amino acid sequence according to SEQ ID NO 13. 
     
     
       12. The recombinant AdB-2/3 fiber polypeptide of  claim 4 , wherein the knob domain comprises an amino acid sequence according to SEQ ID NO 14. 
     
     
       13. The recombinant AdB-2/3 fiber polypeptide of  claim 4 , wherein the knob domain comprises an amino acid sequence selected from the group consisting of SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:4, and SEQ ID NO:10. 
     
     
       14. The recombinant AdB-2/3 fiber polypeptide of  claim 4 , wherein the AdB-2/3 fiber polypeptide further comprises a dimerization domain comprising an amino acid sequence selected from the group consisting of EVSALEK (SEQ ID NO:22) and/or KVSALKE (SEQ ID NO: 23). 
     
     
       15. The recombinant AdB-2/3 fiber polypeptide of  claim 4 , wherein the recombinant AdB-2/3 polypeptide comprises:
 a) one or more shaft domains that each comprise an Ad3 shaft domain (SEQ ID NO:1); and 
 b) a knob domain that comprises an Ad3 knob domain (SEQ ID NO:6). 
 
     
     
       16. The recombinant AdB-2/3 fiber polypeptide of  claim 4 , wherein the AdB-2/3 fiber polypeptide contains a single AdB-2/3 fiber polypeptide shaft domain. 
     
     
       17. The recombinant AdB-2/3 fiber polypeptide of  claim 4 , wherein the AdB-2/3 fiber polypeptide is dimerized. 
     
     
       18. A composition, comprising (a) the recombinant AdB-2/3 fiber polypeptide of  claim 4 , and (b) one or more compounds selected from the group consisting of therapeutics, diagnostics, and imaging agents. 
     
     
       19. The composition of  claim 18 , wherein the one or more compounds comprise at least one therapeutic, wherein the therapeutic is selected from the group consisting of antibodies, immunoconjugates, nanoparticles, chemotherapeutics, radioactive particles, viruses, vaccines, cellular immunotherapy therapeutics, gene therapy constructs, nucleic acid therapeutics, and combinations thereof.